Methylmercury promotes oxidative stress and autophagy in rat cerebral cortex: Involvement of PI3K/AKT/mTOR or AMPK/TSC2/mTOR pathways and attenuation by N-acetyl-L-cysteine

被引:8
作者
Wei, Yanfeng [1 ,3 ]
Ni, Linlin [1 ]
Pan, Jingjing [1 ]
Li, Xiaoyang [1 ]
Deng, Yu [1 ]
Xu, Bin [1 ]
Yang, Tianyao [1 ]
Sun, Jingyi [2 ]
Liu, Wei [1 ]
机构
[1] China Med Univ, Sch Publ Hlth, Dept Environm Hlth, 77 Puhe Rd, Shenyang 110122, Liaoning, Peoples R China
[2] Dalian Med Univ, Hosp 2, Dept Cardiol, 467 Zhongshan Rd, Dalian 116027, Liaoning, Peoples R China
[3] Xian Ctr Dis Control & Prevent, Dept Planned Immunizat, 599 Xiying Rd, Xian 710054, Shaanxi, Peoples R China
关键词
Methylmercury; Oxidative stress; Autophagy; mTOR; NAC; ACETYLCYSTEINE NAC; SCHOOL-AGE; IN-VITRO; EXPOSURE; DAMAGE; CELLS; ROS; NEUROTOXICITY; INHIBITION; MECHANISMS;
D O I
10.1016/j.ntt.2022.107137
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Methylmercury (MeHg) is a potent neurotoxicant that could induce oxidative stress and autophagy. However, the underlying mechanisms through which MeHg affects the central nervous system have not been fully elucidated, and little has been known of the interaction between oxidative stress and autophagy. Therefore, rats were administrated with different MeHg concentrations to evaluate the neurotoxic effects and autophagy in cerebral cortex. Moreover, we have investigated the neuroprotective role of N-acetyl-L-cysteine (NAC) against MeHg-induced neurotoxicity in order to estimate the regulation effects of oxidative stress on autophagy. A total of 64 rats, 40 of which were randomly divided into control and MeHg-treated (4, 8 and 12 mu mol/kg) groups. The remaining 24 rats were divided into control, NAC control (1 mmol/kg), 12 mu mol/kg MeHg, and NAC pre-treatment. Administration of 12 mu mol/kg MeHg significantly increased behavioral and pathological abnor-malities, and autophagy levels. In addition, the oxidative stress levels increased, together with abnormal expression of autophagy-related molecules. Pretreatment with NAC significantly prevented MeHg-induced oxidative stress and PI3K/AKT/mTOR or AMPK/TSC2/mTOR-mediated autophagy. In conclusion, the present study suggested that oxidative stress can regulate autophagy through PI3K/AKT/mTOR or AMPK/TSC2/mTOR pathways. This study provides a theoretical basis for the study and treatment of MeHg-induced neurotoxicity.
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页数:12
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